Enormous progress has been made recently in understanding the age-related structural maturational changes that occur in the human brain during childhood and adolescence, but variability in brain structure is very large, even among individuals of the same chronological age. The literature suggests an offset in development of limbic structures which control affect, emotion, encoding information, which may develop prior to the executive centers (frontal cortices) that provide regulatory control over impulses and risk assessment. Almost nothing is yet known about neurodevelopmental, neuroendocrine, behavioral and environmental factors that likely relate to variability in brain structure and function, and cognitive abilities that change so dramatically during adolescence. In this project, we propose to longitudinally study 120 typically developing adolescents between 9 and 15 years of age with 2-year scan intervals, and to collect brain imaging (structural MRI, diffusion tensor imaging and functional MRI with tasks of response inhibition, reward processing, delayed discounting, facial affect processing), neurocognitive (with emphasis on executive functioning and cognitive control), physical sexual maturation (using Tanners staging), and hormonal (cortisol, testosterone, estrogen and Dehydroepiandrosterone (DHEA) using saliva samples) data as well as measures of daily stress. With these rich multimodal imaging, behavioral, cognitive and hormonal data, we will address the following specific aims: 1) to distinguish hormone-dependent from non-hormone dependent neurodevelopmental effects in adolescence, 2) to evaluate relationships between brain changes and behavioral indices of cognition (cognitive control, executive functions, daily stress) and motivation (e.g., reward sensitivity), and 3) to evaluate gender differences in relationships between brain changes and indices of pubertal progression. To our knowledge, this will be the first study to undertake such challenges by using cutting-edge integrative multimodal image analyses of functional and structural MRI to examine, longitudinally, brain development in adolescents and to distinguish hormonal from other age-related environmental and behavioral correlates. PUBLIC HEALTH RELEVANCE: The proposed research to study adolescent brain development using integrated multimodal neuroimaging, neurocognitive, stress, and hormonal measures longitudinally in typically developing children and adolescents is of the utmost importance. The beginning of adolescence is a time of dramatic physical, emotional and social change, and is also associated with the onset of psychopathology such as depression, suicide, and substance abuse. To provide a framework for understanding how risks during adolescence can tip the balance toward pathological outcomes in youth and adulthood, models of typical brain development need to evaluate interactions between hormonal and physical sexual maturity and the still-maturing neural systems responsible for social interactions, affective states and cognitive control.